Polymer compositions with antimicrobial and wavelength-shifting nanoparticles

ABSTRACT

Disclosed are embodiments of polymer compositions and systems that contain antimicrobial and wavelength-shifting metal nanoparticles. The polymer compositions containing metal nanoparticles protect exposed materials from UV radiation. The polymer compositions containing metal nanoparticles down convert incoming UV light to light that may have a longer wavelength. Unexpectedly, by selecting at least two differently configured nanoparticle components (e.g., different in size, shape, or both), each with specific particle size distribution, it is possible to effectively protect an area from damage resulting from exposure to UV radiation. In addition, spherical silver nanoparticles do not cause bacteria to become resistant as do convention silver nanoparticles made by chemical synthesis.

CROSS-REFERENCE TO RELATED APPLICATION

This application claims the benefit of U.S. Provisional Application No.63/270,272, filed Oct. 21, 2021, which is incorporated by reference inits entirety 0.1609

BACKGROUND Technical Field

This disclosure relates to polymer compositions and systems that containantimicrobial and wavelength-shifting nanoparticles and uses thereof inpolymer manufacturing processes.

Related Technology

Polymers used in medical and other applications are typicallyinexpensive and can be used across many different medical functions.Polymeric articles of manufacture may be manufactured using injectionmolding processes. One of the issues with mold injected polymers is thesurface finish of the end product can be sponge-like, with pores thatcan extend several microns deep into the product. FIG. 1 is a scanningtransmission electron microscope (STEM) image of a surface ofpolystyrene from thermal extruded pellet, which has a high degree ofporosity. This can be a perfect protective breeding ground for bacteriaand microbes to grow and is a big concern for hospitals and insurancepolicy holders. For this reason, the management of polymers used inareas of high sensitivity requires expensive and rigorous sterilizationand storage procedures, which may still result in aggravated tissueswhen the infected polymers are used in delivering substances topatients. Worse, drug resistant bacterial and/or fungal infections maycause expensive healthcare maintenance and even death, if passed topatients from infected polymer products.

The overuse of antibiotics has contributed to an overall antibioticresistance seen in newly discovered strains of microbes. There isconcern that an increase in antibiotic resistance of microbes may leadto “superbugs” that may be unable to be controlled with modern,conventional technologies. Currently, there are few conventional methodsof disinfecting and microbial control without the use of antibiotics.Medical devices that incorporate antibiotics cannot stop infection andformation of biofilms when a patient has microbes with antibioticresistance. In such cases, the use of antibiotics in polymeric materialsdoes not protect the patient from infection and may give a false senseof security.

There are attempts to incorporate ionic colloidal silver and silvernanoparticles into polymeric materials to import antimicrobial activityto polymers. However, antimicrobial resistance has now been discoveredfor colloidal silver (traditional silver nanoparticles made by chemicalprocesses) and ionic silver. McNeilly et al., “Emerging Concern forSilver Nanoparticle Resistance in Acinetobacter baumannii and OtherBacteria,” Front. Microbiol., 16 Apr. 2021, discuss the emergence ofseveral antibiotic-resistant bacteria, including Acinetobacterbaumannii, Enterococcus faecium, Staphylococcus aureus, Klebsiellapneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, andEnterobacter spp. Of these, A. baumannii was of particular concern andwas found to also have developed resistance to silver nanoparticles, aswas E. Coli, Enterobacter cloacae, S. typhimurium, B. subtilis, S.aureus. P. aeruginosa, K. pneumoniae, Serratia marcescens, Acinetobacterspp.

Silver, “Bacterial silver resistance: molecular biology and uses andmisuses of silver compounds,” FEMS Microbiology Reviews, Volume 27,Issue 2-3, June 2003, Pages 341-35, discusses silver-resistantSalmonella, and Escherichia coli. Elkrewi, et al., “Cryptic silverresistance is prevalent and readily activated in certain Gram-negativepathogens,” J. Antimicrob. Chemother., 2017 Nov. 1; 72(11):3043-3046discloses silver nanoparticle resistance by gram negative pathogens,such as Enterobacter spp., Klebsiella spp. Escherichia coli, Pseudomonasaeruginosa, Acinetobacter spp., Citrobacter spp., and Proteus spp.Hosney, “The increasing threat of silver-resistance in clinical isolatesfrom wounds and burns,” Infect Drug Resist. 2019; 12: 1985-2001discusses silver-resistant Klebsiella pneumoniae, Staphylococcus aureus,Escherichia coli, Enterobacter cloacae, Pseudomonas aeruginosa, andAcinetobacter baumannii. Percival, et al., “Bacterial resistance tosilver in wound care, J. Hospital Infection, Vol. 60, Issue 1, May 2005,pp. 1-7, discusses the fear and possibility of silver-resistant microbesin wounds. K

dziora, et al., “Consequences Of Long-Term Bacteria's Exposure To SilverNanoformulations With Different PhysicoChemical Properties,” Intl. J. ofNanomedicine, 2020:15 199-213, discusses silver-resistant gram positiveand gram negative bacteria.

An article entitled “Are Silver Nanoparticles a Silver Bullet AgainstMicrobes?” Jul. 13, 2021,https://news.engineering.pitt.edu/are-silver-nanoparticles-a-silver-bullet-against-microbes/(accessed Oct. 12, 2022), discusses silver nanoparticle resistant E.coli., stating: “‘In the beginning, bacteria could only survive at lowconcentrations of silver nanoparticles, but as the experiment continued,we found that they could survive at higher doses . . . . Interestingly,we found that bacteria developed resistance to the silver nanoparticlesbut not their released silver ions alone.’ The group sequenced thegenome of the E. coli that had been exposed to silver nanoparticles andfound a mutation in a gene that corresponds to an efflux pump thatpushes heavy metal ions out of the cell. ‘It is possible that some formof silver is getting into the cell, and when it arrives, the cellmutates to quickly pump it out . . . . More work is needed to determineif researchers can perhaps overcome this mechanism of resistance throughparticle design.’”

Also, silver nanoparticles made by chemical synthesis have external bondangles and edges where silver ions can be released. Adding metalnanoparticles that release ions into polymers yieldsnanoparticle-impregnated polymers and plastics that are a source ofunwanted metal ions, such as silver ions, which are generally toxic tohuman and animal tissues.

Additionally, exposure to solar radiation can cause weakening and otherstructural damage to polymers. When absorbed by polymers, UV energy mayexcite electrons, creating free radicals that can lead to degradation ofthe plastic. Polymers that have been affected by UV radiation may appearchalky, the surface of the polymer may become brittle, and there may bea noticeable color change on the surface of the polymer. UV-causeddegradation may lead to cracks in the polymer product and may cause theproduct to fail altogether. For example, UV radiation hittingpolypropylene and/or low-density polyethylene may interact with tertiarycarbon bonds within their structures, which can then interact withatmospheric oxygen. This can produce carbonyl groups in the main chainof the structure, leaving the plastic product prone to cracking ordiscoloration.

Ultraviolet radiation B (“UVB radiation”) is generally considered to liewithin the range of about 280 to about 315 nanometers in wavelength.Ultraviolet radiation A (“UVA radiation”) is generally considered to liewithin the range of about 315 to about 400 nanometers in wavelength.Ultraviolet radiation C (UVC) is generally considered to lie within therange of about 100 to about 280 nanometers in wavelength.

In view of the foregoing, there remains a need to find improved polymermaterials that have antimicrobial properties to prevent colonization ofimplanted medical devices and without using metal nanoparticles thatrelease toxic metal (e.g., silver) ions. There also remains a need tofind improved polymer materials that can resist UV damage when exposedto the sun.

SUMMARY

Disclosed are embodiments of polymer compositions and systems that aremodified by incorporating therein antimicrobial and wavelength-shiftingmetal nanoparticles. In some embodiments, the polymer compositionscontaining metal nanoparticles protect exposed materials from UVradiation. In some embodiments, the polymer compositions containingnanoparticles down-convert incoming UV light to light of longerwavelength that are less damaging, or non-damaging, to polymer linkages.

The disclosed polymer compositions modified by incorporating metalnanoparticles also have antimicrobial properties to prevent colonizationof microbes within pores of the polymer materials and structures. Suchnanoparticle-modified polymers do not develop silver nanoparticleantibiotic resistance, as occurs with conventional colloidal silver andsilver nanoparticles made via chemical synthesis. Surprisingly andunexpectedly, it has been found that nonionic silver nanoparticlesformed by laser ablation do not lead to silver nanoparticle resistance,as occurs when using traditional colloidal silver and silvernanoparticles made by chemical synthesis and which are known releasesilver ions as their main mode of antimicrobial activity.

It is proposed that the new unique metal (e.g., silver) nanoparticlesproduced by high energy methods possessing smooth spherical morphologiesand in narrow size distributions can be integrated into moldablepolymers to mitigate bacteria or microbes that may setup around theplastic or within the plastics themselves. A method for adding the metalnanoparticles to the polymers in a non-interruptive process before theparts are made is also disclosed. Unexpectedly, spherical-shaped silvernanoparticles made by laser ablation and having a narrow particle sizedistribution do not result in microbial resistance, thus solving atremendous problem with traditional antibiotics, silver compounds,colloidal silver, and silver nanoparticles.

In some embodiments, a metal nanoparticle composition may comprise (1) acarrier and (2) a plurality of metal (e.g., silver and/or gold)nanoparticles having a particle size and a particle size distributionselected so as to selectively and preferentially kill a target microbeselected from bacteria, fungi, and viruses.

Where the targeted microbe is a bacterium, anti-bacterial polymercompositions can include spherical metal (e.g., silver) nanoparticleshaving a particle size in a range of about 3 nm to about 14 nm, or about5 nm to about 13 nm, or about 7 nm to about 12 nm, or about 8 nm toabout 10 nm. Within these size ranges it is possible to select “designeranti-bacterial particles” of specific size that are particularlyeffective in targeting a specific bacterium.

Where the targeted microbe is a fungus, anti-fungal polymer compositionscan include spherical metal (e.g., silver) nanoparticles having aparticle size in a range of about 9 nm to about 20 nm, or about 10 nm toabout 18 nm, or about 11 nm to about 16 nm, or about 12 nm to about 15nm. Within these size ranges it is possible to select “designeranti-fungal particles” of specific size that are particularly effectivein targeting a specific fungus.

Where the targeted microbe is a virus, anti-viral polymer compositionscan include metal (e.g., silver) nanoparticles having a particle size ina range of about 8 nm or less, or about 1 nm to about 7 nm, or about 2nm to about 6.5 nm, or about 3 nm to about 6 nm. Within these sizeranges it is possible to select “designer anti-viral particles” ofspecific size that are particularly effective in targeting a specificvirus.

In some embodiments, spherical metal (e.g., silver) nanoparticles havinga mean diameter (number average) and a particle size distribution inwhich at least 99% of the spherical metal nanoparticles have a particlesize within 30% of the mean diameter, or within 20% of the meandiameter, or within 10% of the mean diameter and/or wherein at least 99%of the spherical metal nanoparticles have a diameter within ±3 nm of themean diameter, or within ±2 nm of the mean diameter, or within ±1 nm ofthe mean diameter.

In some embodiments, the compositions may comprise coral-shaped metalnanoparticles in addition to the spherical metal nanoparticles.Coral-shaped metal (e.g., gold) nanoparticles have a non-uniform crosssection and a globular structure formed by multiple, non-linear strandsjoined together without right angles. In some cases, the coral-shapedmetal nanoparticles can be used to potentiate the effect of sphericalmetal (e.g., silver) nanoparticles.

In some embodiments, metal nanoparticles can comprise at least one metalselected from the group consisting of silver, gold, platinum, palladium,rhodium, osmium, ruthenium, rhodium, rhenium, molybdenum, copper, iron,nickel, tin, beryllium, cobalt, antimony, chromium, manganese,zirconium, tin, zinc, tungsten, titanium, vanadium, lanthanum, cerium,heterogeneous mixtures thereof, and alloys thereof. Nanoparticlescomprised of silver, gold, and mixtures and alloys thereof can beparticularly effective.

Examples of metal (e.g., silver and gold) nanoparticles and nanoparticlecompositions that can be used herein are disclosed in U.S. Pat. Nos.9,849,512, 9,434,006, 9,919,363, 10,137,503, and 10,610,934, which areincorporated herein by reference.

In some embodiments, polymer compositions can be made from thermoplasticmaterials in which metal nanoparticles are incorporated therein, such asby coating polymer beads or pellets that are later thermoplasticallyformed into a desired structure of article of manufacture. In otherembodiments, polymer compositions can be made from two-partcompositions, where metal nanoparticles are included in one or bothparts of the composition. In both cases, the metal nanoparticles becomemixed throughout the polymer composition, either when in a molten stateprior to molding and cooling or in a liquid state prior to molding andthermosetting.

In some embodiments, a method of protecting exposed materials from UVradiation comprises: (1) applying a polymer composition comprising acarrier and metal nanoparticles onto a substrate, and (2) the polymercomposition reflecting and/or down converting at least a portion of theUV light incident upon the area.

In some embodiments, metal nanoparticles can comprise spherical-shapedmetal (e.g., silver) nanoparticles and/or coral-shaped metal (e.g.,gold) nanoparticles. In some embodiments the coral-shaped metalnanoparticles can be used together with spherical-shaped metalnanoparticles (e.g., in order to potentiate the spherical-shaped metalnanoparticles).

In some embodiments, nanoparticle compositions, such as single- andmulti-component nanoparticle compositions, include a stabilizing agentcapable of holding the nanoparticles in solution while still maintainingthe functionality of the nanoparticles. In some embodiments, the metalnanoparticles are sprayed or coated onto already made packagingmaterials. In some embodiments, the metal nanoparticles are embeddedinto the package materials, such as thermoplastic wraps, polystyrenetrays, solid plastics, polyurethanes, etc.

To manufacture shaped products from thermoplastic polymers, polymergranules used to mold polymeric articles of manufacture can be coatedwith metal (e.g., silver and/or gold) nanoparticles, such as bydispersing the metal nanoparticles in a volatile solvent, applying thedispersion to the polymer granules, and allowing the solvent toevaporate. When the metal nanoparticle-coated polymer granules areheated into a molten state within forming equipment, such as an auger,extruder, or injection molding machine, the metal nanoparticles becomedistributed throughout the molten thermoplastic polymer and the plasticmaterials and articles made therefrom.

In the case of two-part curable resins used to make thermoset polymerproducts, metal nanoparticles can be included in one or both parts ofthe two-part system. When the two parts are mixed together, the metalnanoparticles are blended throughout the mixture and will solidify inplace within whatever product or article the composition is shaped into.

The portion of metal nanoparticles on the surface of the polymermaterial and/or embedded within pores in communication with the polymersurface will provide antimicrobial activity to prevent microbial growthon the surface of the polymer material. The metal nanoparticles willalso protect the polymers materials from damage by UV radiation bydown-converting incoming UV energy to a lower energy wavelength(s) thatis less damaging, or non-damaging, to the polymer material.

Nonionic silver nanoparticles made by laser ablation so as to have noexternal bond angles and edges, and which do not release detectablequantities of silver ions when exposed to water, are already known topass the EPA's sanitization surface tests using the nanoparticles inwater as a spray on product. Polymer materials disclosed herein, withnanoparticles embedded inside, is a new approach allowing for surfacewear to not deplete the nanoparticles available, even after abrasion ormachining. Filaments were tested directly and test subjects similar tothe peni-cylinders used in the surface sanitization programs were testedwith accepted methods for measuring effective bacteria control.

This summary is provided to introduce a selection of concepts in asimplified form that are further described below in the detaileddescription. This summary is not intended to identify key features oressential features of the claimed subject matter, nor is it intended tobe used as an indication of the scope of the claimed subject matter.

BRIEF DESCRIPTION OF THE DRAWINGS

Various objects, features, characteristics, and advantages of theinvention will become apparent and more readily appreciated from thefollowing description of the embodiments, taken in conjunction with theaccompanying drawings and the appended claims, all of which form a partof this specification. In the Drawings, like reference numerals may beutilized to designate corresponding or similar parts in the variousFigures, and the various elements depicted are not necessarily drawn toscale, wherein:

FIG. 1 is a scanning transmission electron microscope (STEM) image of asurface of polystyrene from thermal extruded pellets;

FIGS. 2A-2C are STEM images that illustrate thermoplastics containingsilver (Ag) nanoparticles;

FIGS. 3A-B schematically illustrate a microbe after having absorbedspherical-shaped metal nanoparticle from a substrate and disulfide bondsbeing catalytically denatured by a spherical-shaped nanoparticle;

FIG. 4 illustrates a STEM image of silver (Ag) nanoparticles inside aMRSA SA62 drug resistant bacteria;

FIGS. 5A-5C illustrate STEM images of Tecoflex EG-93A-B20 thermoplasticpolymer embedded with silver nanoparticles;

FIGS. 6A-6C illustrate STEM images of Isoplast 2510 thermoplasticpolymer embedded with silver nanoparticles;

FIG. 7A illustrates industrial thermoplastic pellets that have beentreated with silver (Ag) nanoparticles;

FIG. 7B illustrates an extruded filament from thermoplastic pellets suchas those illustrated in FIG. 7A; and

FIGS. 8A-8B illustrate a close-up STEM image of an embeddedspherical-shaped silver (Ag) nanoparticle in a thermoplastic material.

DETAILED DESCRIPTION

Disclosed are embodiments of polymer compositions and systems thatcontain antimicrobial and wavelength-shifting metal nanoparticles. Insome embodiments, the polymer compositions containing metalnanoparticles protect exposed materials from UV radiation. In someembodiments, the polymer compositions containing metal nanoparticlesdown-convert incoming UV light to light having a longer wavelength. Insome embodiments, the polymer compositions containing metalnanoparticles have antimicrobial properties. Surprisingly andunexpectedly, nonionic silver nanoparticles formed by laser ablation donot lead to silver nanoparticle resistance, as occurs when usingconventional colloidal silver and silver nanoparticles made by chemicalsynthesis and which are known to release silver ions as their main modeof antimicrobial activity.

In some embodiments, by selecting at least two differently configurednanoparticle components (e.g., different in size, shape, or both), eachwith specific particle size distribution, and stabilizing those at leasttwo nanoparticle components with a stabilizing agent (such asnatural-based polyphenol or other cream or gel or other surfactant), itis possible to effectively protect an area from damage resulting fromexposure to UV radiation.

I. INTRODUCTION

The term “nanoparticle” often refers to particles having a largestdimension of less than 100 nm. Bulk materials typically have constantphysical properties regardless of size, but at the nanoscale, sizedependent properties are often observed. Thus, properties of materialschange as their size approaches the nanoscale and as the percentage ofatoms at the surface of a material becomes significant. For bulkmaterials larger than one micrometer (or micron), the percentage ofatoms at the surface is insignificant in relation to the number of atomsin the bulk of the material. The interesting and sometimes unexpectedproperties of nanoparticles are therefore largely due to the largesurface area of the material, which dominates the contributions made bythe relatively small bulk of the material.

The ability to select and use metal nanoparticles that can targetspecific types or classes of microbes provides a number of benefits. Inthe case where only certain nanoparticle sizes are effective in killinga particular microbe or class of microbes, providing metal nanoparticleswithin a narrow particle size distribution of the correct particle sizemaximizes the proportion of nanoparticles that are effective in killingthe target microbe and minimizes the proportion of nanoparticles thatare less effective, or ineffective, in killing the target microbe. This,in turn, greatly reduces the overall amount or concentration ofnanoparticles required to provide a desired kill- or deactivation rateof a targeted microbe. Eliminating improperly sized nanoparticles alsoreduces the tendency of the composition to kill or harm non-targetedmicrobes or other cells, such as healthy mammalian or human cells. Inthis way, highly specific antimicrobial compositions can better target aharmful microbe while being less harmful or even non-toxic to humans,animals, and plants.

Moreover, because it has now been discovered that the nonionic metalnanoparticles formed by laser ablation do not result in antimicrobialresistance, which is unexpected given the extensive data for othersilver nanoparticles, the concentration of silver nanoparticles requiredto effectively kill microbes remains essentially the same over time.This is in contrast to silver nanoparticles made by chemical processes,which have external bond angles and typically release silver ions aspart of their antimicrobial activity. When antimicrobial resistance toconventional silver nanoparticles develops, increasing concentrations ofsuch nanoparticles are necessary to maintain the ability to killmicrobes.

In some embodiments, a metal nanoparticle composition may comprise (1) apolymer and/or polymeric structure or article of manufacture and (2) aplurality of metal nanoparticles having a particle size and a particlesize distribution selected so as to selectively and preferentially killa target microbe selected from bacteria, fungi, and viruses. The metalnanoparticles are advantageously nonionic, ground state, with noexternal edges or bond angles that can release metal ions. Sphericalmetal nanoparticles are typically used to kill microbes, althoughcoral-shaped metal nanoparticles can provide anti-microbial activity,typically in combination with spherical metal nanoparticles.

In some embodiments, the metal nanoparticles may comprise or consistessentially of nonionic, ground state metal nanoparticles with noexternal edges or bond angles that can release metal ions. Examplesinclude spherical metal nanoparticles, coral-shaped metal nanoparticles,and blends of spherical metal nanoparticles and coral-shaped metalnanoparticles.

The metal nanoparticles, including spherical and coral-shapednanoparticles, may comprise any desired metal, mixture of metals, ormetal alloy, including at least one of silver, gold, platinum,palladium, rhodium, osmium, ruthenium, rhodium, rhenium, molybdenum,copper, iron, nickel, tin, beryllium, cobalt, antimony, chromium,manganese, zirconium, tin, zinc, tungsten, titanium, vanadium,lanthanum, cerium, heterogeneous mixtures thereof, or alloys thereof.Nanoparticles comprised of silver, gold, and mixtures and alloys thereofcan be particularly effective.

Absorption of solar radiation is much higher in materials composed ofnanoparticles than it is in thin films of continuous sheets of material.In both solar PV and solar thermal applications, by controlling thesize, shape, and material of the particles, it is possible to controlsolar absorption. The size-dependent property changes of nanoparticlesinclude quantum confinement in semiconductor particles, surface plasmonresonance in some metal particles, and super-para-magnetism in magneticmaterials.

In some embodiments, gold (Au) nanoparticles are included in the polymercompositions to down-shift incoming UV radiation. The gold nanoparticlesmay down-convert the light waves into less energetic and harmful lightof longer wavelength(s). The gold nanoparticles may down-convert thelight wavelengths towards the red zone of the light spectrum. In someembodiments, the gold nanoparticles are spherical. In some embodiments,the gold nanoparticles are approximately 1 to 40 nm in diameter.

In some embodiments, silver (Ag) nanoparticles are included in thepolymer compositions to impart antimicrobial properties to the polymercompositions. The silver nanoparticles may be engulfed or ingested bymicrobes, and the silver nanoparticles may disrupt vital proteins of themicrobe, effectively deactivating or killing the microbe. In someembodiments, the silver nanoparticles are spherical. In someembodiments, the silver nanoparticles are approximately 1 to 10 nm indiameter.

Examples of metal nanoparticles and nanoparticle compositions that canbe used herein are disclosed in U.S. Pat. Nos. 9,849,512, 9,434,006,9,919,363, 10,137,503, and 10,610,934, which are incorporated herein byreference.

II. PLASTICS MANUFACTURING

Some common plastics manufacturing processes are extrusion and injectionmolding. Many medical thermoplastics are manufactured using one of thetwo processes. In the extrusion process, polymeric pellets or granulesare fed into an extrusion machine by a hopper. The polymeric pellets orgranules are heated and melted inside a barrel, sometimes with the aidof an auger. The melted polymer is then pushed through a metal die by ascrew auger, creating a fixed, continuous shape. The resulting polymerobject can be cut or trimmed as desired. The extrusion process iscommonly used for manufacturing pipes, tubes, frames, symmetricaldevices, etc.

Injection molding involves injecting a molten thermoplastic polymer intoa pre-existing mold. The molten thermoplastic polymer can be formed byheating polymeric pellets or granules. Once injected into the mold, thepolymer will cool and harden into its final shape. The molten polymer isgenerated similarly to the extrusion process—polymer pellets or granulesare fed into a barrel or other chamber by a hopper where they are thenheated (and melted). A combination extrusion-injection molding processmay be used when a hollow product is desired.

Additives may be included in the plastic pellets or granules, which aremelted down to create the final products. Colorants, stiffeners, andother enhancers may be sprayed or coated onto the pellets prior toheating. For example, colorants are often dissolved or dispersed in avolatile solvent and then sprayed onto the pellets. Upon heating, thevolatile solvent will evaporate off, leaving the colorant evenlydistributed among the pellets. The colorant will get evenly incorporatedinto the melted plastic and result in a uniformly colored product. Otheradditives may similarly be incorporated into the final plastic products.

Thermoset polymers are also useful materials that can be molded orshaped into a desired object. Rather than being heated to above themelting point, thermoset polymers are typically formed by mixing two ormore initial separate components that are formulated to react togetherto form an initial mixture that is flowable. The flowable mixture can bemolded into a desired shape in similar fashion as thermoplasticmaterials. The components in the thermoset composition react together tocause polymerization and/or cross-linking to form a solidified thermosetpolymer.

Examples of common materials for manufacturing medical devices and otherpolymer objects or configurations include silicone, epoxies, polystyrene(PS), polyethylene (PE), ethylene-vinyl acetate copolymer (EVA),polycarbonate (PC), polyurethane (PU), polyether ether ketone (PEEK),polylactic acid (PLA), polyester (PES), polypropylene (PP), polyethyleneterephthalate (PET), polybutylene terephthalate (PBT),phenol-formaldehyde (PF), nylon or polyimides (PA), melamineformaldehyde (MF), polytetrafluoroethylene (PTFE), polyvinyl chloride(PVC), acrylonitrile butadiene styrene terpolymers (ABS), Kevlar, andcarbon fiber-reinforced polymers. Thermoplastics, such as PE and PVC,may be melted and heated multiple times during plastics manufacturing.Thermoset plastics, such as PU and silicone, remain solid after a curingprocess has set the plastic.

III. NANOPARTICLE COMPOSITIONS

Metal nanoparticles and nanoparticle compositions typically includenonionic, ground state, metal nanoparticles with no external edges orbond angles that can otherwise release metal ions. Nanoparticlecompositions may include spherical metal nanoparticles, coral-shapedmetal nanoparticles or a combination of the two. Spherical metalnanoparticles are typically used to kill microbes, although coral-shapedmetal nanoparticles can provide anti-microbial activity, typically incombination with spherical metal nanoparticles.

Nonionic, ground state, spherical metal nanoparticles with no externaledges or bond angles that can otherwise release metal ions, andcompositions containing such nanoparticles, can be made according to thedisclosure of U.S. Pat. Nos. 9,849,512, 10,137,503, and 10,610,934.Nonionic, ground state, coral-shaped metal nanoparticles with noexternal edges or bond angles that can otherwise release metal ions, andcompositions containing such nanoparticles, can be made according to thedisclosure of U.S. Pat. No. 9,919,363. Compositions that contain amixture of spherical metal nanoparticles and coral-shaped metalnanoparticles are disclosed in U.S. Pat. No. 9,434,006. The foregoingpatents are incorporated herein by reference in their entirety

Where the targeted microbe is a bacterium, anti-bacterial polymercompositions can include spherical metal nanoparticles having a particlesize in a range of about 3 nm to about 14 nm, or about 5 nm to about 13nm, or about 7 nm to about 12 nm, or about 8 nm to about 10 nm. Withinthese size ranges it is possible to select “designer anti-bacterialparticles” of specific size that are particularly effective in targetinga specific bacterium.

Where the targeted microbe is a fungus, anti-fungal polymer compositionscan include spherical metal nanoparticles having a particle size in arange of about 9 nm to about 20 nm, or about 10 nm to about 18 nm, orabout 11 nm to about 16 nm, or about 12 nm to about 15 nm. Within thesesize ranges it is possible to select “designer anti-fungal particles” ofspecific size that are particularly effective in targeting a specificfungus.

Where the targeted microbe is a virus, anti-viral polymer compositionscan include metal nanoparticles having a particle size in a range ofabout 8 nm or less, or about 1 nm to about 7 nm, or about 2 nm to about6.5 nm, or about 3 nm to about 6 nm. Within these size ranges it ispossible to select “designer anti-viral particles” of specific size thatare particularly effective in targeting a specific virus.

In some embodiments, nanoparticle polymer compositions may includenanoparticles in a concentration of about 50 ppb to about 100 ppm, orabout 100 ppb to about 50 ppm, or about 200 ppb to about 20 ppm, orabout 400 ppb to about 10 ppm, or about 600 ppb to about 6 ppm, or about800 ppb to about 4 ppm, or about 1 ppm to 3 ppm, or about 2 ppm byweight of the polymer composition. The compositions may includenanoparticles in a concentration range with endpoints defined by any twoof the foregoing values of this paragraph.

a. Multi-Component Nanoparticle Compositions

In some embodiments, coral-shaped metal nanoparticles can be used inconjunction with spherical metal nanoparticles. In general, sphericalmetal nanoparticles can be smaller than coral-shaped metal nanoparticlesand in this way can provide very high surface area for catalyzingdesired reactions or providing other desired benefits. On the otherhand, the generally larger coral-shaped nanoparticles can exhibit highersurface area per unit mass compared to spherical nanoparticles becausecoral-shaped nanoparticles have internal spaces and surfaces rather thana solid core and only an external surface.

In some cases, providing nanoparticle compositions containing bothspherical and coral-shaped nanoparticles can provide synergisticresults. For example, coral-shaped nanoparticles can help carry and/orpotentiate the activity of spherical nanoparticles in addition toproviding their own unique benefits. For example, smaller particles mayoffer better relative protection against UVB radiation, while relativelylarger particles may offer better protection against UVA radiation. Insome embodiments, a combination of spherical and coral-shapednanoparticles can lead to synergistic, broad-spectrum protection with agreater amount of protection (e.g., amount of UV radiation reflected)per amount of active ingredient relative to single sized and/or shapedcompositions.

In some embodiments, the mass ratio of spherical nanoparticles tocoral-shaped nanoparticles in the nanoparticle composition can be in arange of about 1:1 to about 50:1, or about 2.5:1 to about 25:1, or about5:1 to about 20:1, or about 7.5:1 to about 15:1, or about 9:1 to about11:1, or about 10:1. The particle number ratio of sphericalnanoparticles to coral-shaped nanoparticles in the nanoparticlecomposition can be in a range of about 10:1 to about 500:1, or about25:1 to about 250:1, or about 50:1 to about 200:1, or about 75:1 toabout 150:1, or about 90:1 to about 110:1, or about 100:1.

In some embodiments, spherical metal nanoparticles can have a diameterof about 40 nm or less, about 35 nm or less, about 30 nm or less, about25 nm or less, about 20 nm or less, about 15 nm or less, about 10 nm orless, about 7.5 nm or less, or about 5 nm or less. The spherical metalnanoparticles can have a particle size distribution wherein at least 99%of the metal nanoparticles have a particle size within 30% of the meandiameter, or within 20% of the mean diameter, or within 10% of the meandiameter and/or wherein at least 99% of the spherical-shapednanoparticles have a diameter within ±3 nm of the mean diameter, orwithin ±2 nm of the mean diameter, or within ±1 nm of the mean diameter.The spherical nanoparticles can have a potential of at least about ±10mV (absolute value), or at least about ±15 mV, or at least about ±20 mV,or at least about ±25 mV, or at least about ±30 mV.

In some embodiments, at least a portion of the spherical and/orcoral-shaped nanoparticles can comprises at least one metal selectedfrom the group consisting of gold, platinum, silver, palladium, rhodium,osmium, ruthenium, rhodium, rhenium, molybdenum, copper, iron, nickel,tin, beryllium, cobalt, antimony, chromium, manganese, zirconium, tin,zinc, tungsten, titanium, vanadium, lanthanum, cerium, heterogeneousmixtures thereof, and alloys thereof. Nanoparticles comprised of silver,gold, and mixtures and alloys thereof can be particularly effective.

In some embodiments, at least one of either the first or second set ofmetal nanoparticles is selected so as to selectively reflect, block,and/or scatter a particular range of solar radiation. For example, thefirst set of metal nanoparticles may be selected as spherical-shapedmetal nanoparticles having a smaller relative size and which thereforeselectively reflect, scatter, and/or block more particularly UVBradiation, and a second set of metal nanoparticles may be selected ascoral-shaped metal nanoparticles having a larger relative size and whichtherefore selectively reflect, scatter, and/or block more particularlyUVA radiation. In other embodiments, the first and second set ofnanoparticles may be both spherical or may be both coral-shaped, buthave different sizes and/or size distributions.

In some embodiments, the compositions will include at least onespherical anti-microbial nanoparticle component and larger coral-shapednanoparticle component. In these embodiments, the at least one selectedspherical nanoparticle component will be present in the composition in arange of between about 1 and about 15 ppm (e.g., at least 1 and at most15 ppm) and more particularly in the range of between bout 1 and about 5ppm (e.g., at least 1 and at most 5 ppm). Additionally, in someembodiments, the larger coral-shaped nanoparticles will be present inthe solution in a range of between about 1 and about 5 ppm (e.g., atleast 1 and at most 5 ppm) and more particularly between about 1 andabout 3 ppm (e.g., at least 1 and at most 3 ppm). It should beunderstood that the upper concentration is not restricted as much byefficacy, but more by product formulation cost. Thus, in otherembodiments, the spherical-shaped nanoparticle component may present ata concentration above 5 ppm and/or the coral-shaped nanoparticlecomponent may be present at a concentration above 3 ppm.

In some embodiments, compositions containing metal nanoparticles may beutilized in a plastics manufacturing process to produce plastic productswith embedded nanoparticles. In some embodiments, compositionscontaining the metal nanoparticles are applied retroactively toproducts. For example, the composition may be a coating to be applied onthe inside of plastic tubing. The composition may be coated onto theplastic tubing and provide antimicrobial and UV protection benefits.

IV. ANTIBACTERIAL ACTIVITY OF NANOPARTICLES

FIGS. 2A-2C are STEM images that illustrate thermoplastics containingsilver (Ag) nanoparticles, which provides the polymer composition withantimicrobial and/or wavelength shifting properties.

FIGS. 3A-3B and 4 schematically illustrate a microbe after havingabsorbed spherical-shaped metal nanoparticles from a substrate and thesubsequent denaturation of microbial proteins. FIGS. 3A-3B schematicallyillustrate a microbe after having absorbed spherical-shaped metalnanoparticle from a substrate and disulfide bonds being catalyticallydenatured by a spherical-shaped nanoparticle.

FIG. 4 illustrates a STEM image of silver (Ag) nanoparticles inside aMRSA SA62 drug resistant bacterium. The STEM image in coordination withElectron Diffraction Spectroscopy provided confirmation of the sulfurstripping from the exposed site of disulfide bonds and ferredoxins.

FIG. 3A schematically illustrates a microbe 608 having absorbedspherical-shaped nanoparticles 604 from a solid substrate 602, such asby active absorption or other transport mechanism. Alternatively,spherical-shaped nanoparticles 604 can be provided in a composition (notshown), such as in a liquid or gel carrier. The nanoparticles 604 canfreely move throughout the interior 606 of microbe 608 and come intocontact with one or more vital proteins or enzymes 610 that, ifdenatured, will kill or disable the microbe.

One way that nanoparticles may kill or denature a microbe is bycatalyzing the cleavage of disulfide (S—S) bonds within a vital proteinor enzyme. FIG. 3B schematically illustrates a microbe protein or enzyme710 with disulfide bonds being catalytically denatured by an adjacentspherical-shaped nanoparticle 704 to yield denatured protein or enzyme712. In the case of bacteria or fungi, the cleavage of disulfide bondsand/or cleavage of other chemical bonds of vital proteins or enzymes mayoccur within the cell interior and thereby killing the microbe in thismanner. Such catalytic cleavage of disulfide (S—S) bonds is facilitatedby the generally simple protein structures of microbes, in which manyvital disulfide bonds are on exposed and readily cleaved by catalysis.

Another potential mechanism by which metal (e.g., silver) nanoparticlescan kill microbes is through the production of active oxygen species,such as peroxides, which can oxidatively cleave protein bonds, includingbut not limited to amide bonds.

Notwithstanding the lethal nature of nonionic metal nanoparticlesrelative to microbes, they are essentially harmless and non-toxic tohumans, mammals, and healthy mammalian cells, which contain much morecomplex protein structures compared to simple microbes in which most orall vital disulfide bonds are shielded by other, more stable regions ofthe protein. In many cases the nonionic nanoparticles do not interactwith or attach to human or mammalian cells and can be quickly and safelyexpelled through the urine without damaging kidneys or other cells,tissues, or organs.

In the particular case of silver (Ag) nanoparticles, the interaction ofthe silver (Ag) nanoparticle(s) within a microbe has been demonstratedto be particularly lethal without the need to rely on the production ofsilver ions (Ag⁺) to provide the desired antimicrobial effects, as istypically the case with conventional colloidal silver compositions. Theability of silver (Ag) nanoparticles to provide effective microbialcontrol without any significant or actual release of toxic silver ions(Ag⁺) into the patient or the surrounding environment is a substantialadvancement in the art. Whatever amount or concentration of silver ionsreleased by silver nanoparticles, if any, is well below known orinherent toxicity levels for animals, such as mammals, birds, reptiles,fish, and amphibians.

The nonionic silver nanoparticles made using laser ablation disclosedherein have advantages over convention silver nanoparticles, which areknown to cause antimicrobial silver nanoparticle resistance.Conventional or traditional silver nanoparticles are made according tovarious chemical synthesis methods. The nanoparticles formed using thesevarious chemical synthesis methods tend to exhibit a clustered,crystalline, faceted, or hedron-like shape rather than a true sphericalshape with round and smooth surfaces. Clustered nanoparticles can have arelatively broad size distribution. Silver nanoparticles can have roughsurface morphologies with many edges, such as being hedron shaped asopposed to a truly spherical shape. In some cases, silver nanoparticlesare formed as shells of silver formed over a non-metallic seed material.

As discussed in the Background section, conventional silvernanoparticles made using chemical processes are known to causeantimicrobial resistance, meaning their effective in killing microbesdiminishes over time. Some studies have shown microbial resistance toionic silver in only 6 passages or generations.

In contrast to conventional nanoparticles such made using chemicalsynthesis, which lose their antimicrobial effectiveness over time to avariety of bacteria and other microbes, the spherical-shapednanoparticles formed by laser ablation described herein are solid metal,substantially unclustered, optionally exposed/uncoated, and have asmooth and round surface morphology along with a narrow sizedistribution. They have been shown to have stable anti-microbialactivity even after 28 passages, with no diminution of antimicrobialactivity, such as no reduction in the MIC (minimum inhibitoryconcentration).

In some embodiments, the nanoparticle composition includes nanoparticlesin a concentration of 1 to 2 mg/L (1 to 2 ppm). In some embodiments, thecomposition also includes sodium laurel sulfate (SLS) at levels that arenot antimicrobial. When SLS is mixed with silver nanoparticles, thesilver nanoparticles have significantly higher antimicrobial effect.This is because the SLS encourages the uptake of nanoparticlesassociated with SLS into bacteria or other microbes.

V. NANOPARTICLES—UV PROTECTION

Metal nanomaterials of the type disclosed herein and having diameters orsizes in the range of 10 to 40 nm have loose dielectric fields. When alarge quantity of particles are together, the dielectric effect on lightwaves passing through does not attenuate but can be frequency-shiftedeither to the red or to the blue end of the electromagnetic spectrum.Polymer compositions that have a sufficient quantity of nanoparticlescan effect the UV rays and shift them to the red end of the spectrum toreduce entry of photonic energy at a level that reduces overall damage.

In some embodiments, the polymer compositions can include metalnanoparticles having a high refractive index in order to reflect and/orscatter incident UV radiation. For example, nanoparticles and/ormulti-component nanoparticles used in polymer compositions of thepresent disclosure can have a refractive index for UVA and/or UVBradiation of about 1.5 to about 4.6, or from about 2.0 to about 4.0, orfrom about 2.5 to about 3.5. In some embodiments, the refractive indexof the nanoparticles and/or multi-component nanoparticles will be higherwith respect to UVB radiation relative to UVA radiation (e.g., therefractive index increases with decreasing wavelength). In otherembodiments, however, the refractive index of the nanoparticles and/ormulti-component nanoparticles will be lower with respect to UVBradiation relative to UVA radiation (e.g., the refractive indexincreases with increasing wavelength).

In some embodiments, the polymer compositions can include nanoparticleshaving a photostability such that upon exposure to solar radiation(e.g., in an environment with a relatively high UV index of about 15),the nanoparticles and/or multi-component nanoparticles do not degrade orlose effectiveness in protecting against UV radiation (e.g., remainabout 100% as effective, or remain about 95-100% as effective, or about90-100% as effective, or about 80-100% as effective) over at least agiven time period (e.g., about 1 hour, or about 2-4 hours, or about 4-6hours, about 6-12 hours or longer, or even indefinitely).

In some embodiments, a polymer composition exhibits radiation protectionproperties. For example, some embodiments include a plurality ofnanoparticles (e.g., beryllium and/or gold) configured to absorb harmfulradiation (e.g., alpha particles, beta particles, and/or gammaradiation), thereby reducing or eliminating an amount of radiationpassing through the nanoparticle treated material.

In some embodiments, gold nanoparticles uniformly dispersed throughout aplastics material down-convert incoming UV radiation into less harmfulUV radiation. In some embodiments, the gold nanoparticles may down-shiftincoming UV radiation by at least about 50 nm, or at least about 100 nm,or at least about 150 nm, such as by approximately 200 nm. In someembodiments, the gold nanoparticles may down-shift incoming UV radiationfrom UV light to visible light. In some embodiments, the goldnanoparticles may down-shift incoming UV radiation from UV wavelengthstoward red and/or green wavelengths.

In some embodiments, gold nanoparticles uniformly dispersed throughout apolymer composition may absorb incoming UV radiation at a high energyand emit a lower energy wavelength, thereby imparting UV protection tothe polymer composition and products made therefrom. Unexpectedly, theability of the gold nanoparticles produced by methods outlined in U.S.Pat. No. 9,434,006 B2, incorporated herein by reference, to perpetuallyperform this down-shift in wavelength/radiation energy does notdeteriorate with use. That is, the gold nanoparticles retain their UVprotection capabilities indefinitely and are not degraded by incoming UVradiation. This beneficially prolongs the effectiveness of the polymercomposition and plastic products made therefrom. This also means thatlower concentrations of gold nanoparticles, or other wavelength-shiftingmetal nanoparticles, may be used resulting in products that are cheaperto produce while maintaining their integrity.

VI. METHOD OF MANUFACTURING NANOPARTICLE EMBEDDED POLYMERS

Methods of adding nanoparticles to polymers in a non-interruptive mannerare disclosed. Due to the methods of making the metal nanoparticles(referenced above), they can be produced in liquids directly applicableto polymer pellets or granules. For example, nanoparticles formed bylaser-ablation (such as those described in U.S. Pat. Nos. 9,849,512 B2,9,434,006 B2 and/or 9,919,363 B2) may be dispersed in a solvent, such asethanol, isopropyl alcohol, or acetone, and applied to polymer pelletsor granules prior to an extrusion or injection molding process. When thepolymer pellets or granules coated with the nanoparticles are heated,for example before or during extrusion or injection molding processes,the solvent will evaporate off and the nanoparticles will be uniformlyincorporated into the resulting molten plastic. The solvent may be avolatile solvent, gaseous solvent, or other appropriately evaporativesolvent.

The resulting molten polymer containing a uniform dispersion ofnanoparticles may then be used in extrusion, injection molding or otherplastics processes to manufacture polymer-based products. The endpolymer-based product will contain a uniform dispersion of nanoparticlesthroughout the entirety of the product. For example, tubing made fromthe molten polymer would contain a uniform distribution of nanoparticlesenabled to be antimicrobial and to protect the tubing from UV radiation.

The polymer-based medical device or other article of manufacture will beprotected from UV radiation and microbial growth. The metalnanoparticles embedded into the polymer-based device or article arecapable of down-converting incoming UV radiation to lower energyradiation. This beneficially prevents general degradation of thepolymer-based device or article from UV radiation. The polymer-baseddevices or articles will be able to be used for longer periods of timewithout cracking, discoloration, fogging, leakage, and/or failingcompletely.

Metal nanoparticles are also capable of deactivating or killingmicrobes, preventing microbial build up inside the polymer-basedproducts. This beneficially prolongs to use of polymer-based products,particularly in medical circumstances (such as in hospitals or clinics).This also prolongs the sterilization of the polymer-based products,leading to lower costs in storage and sterilization procedures.

VII. Examples Example 1

Metal nanoparticles (silver and/or gold) were suspended in 99.9%isopropyl alcohol. Inductive Coupled Plasma Optical EmissionSpectrophotometry (ICPOES) was used to verify nanoparticleconcentration. Dynamic Light Scattering (DLS) was used to verifynanoparticle size, which was found to be approximately 6 to 10 nm. STEMimaging with Electron Loss Spectroscopy (ELS) verified surfacecomposition and shorter bond lengths.

Drug resistant bacteria were found to be killed in concentration rangesof 0.5 mg/L (0.5 ppm) to 2 mg/L (2 ppm) of nanoparticles. The highestconcentration found to kill drug resistant bacteria was 8 mg/L (8 ppm).STEM imaging using no stain and a dark field camera with 3 nm of carboncoating allowed for tracking of the nanoparticles within and around abacterium (see FIG. 4 ). The STEM imaging in conjunction with ElectronDiffraction Spectroscopy (EDS) provided confirmation of the sulfurstripping from the exposed site of disulfide bond and ferredoxins.

Example 2

Polyethylene (PE) embedded with silver nanoparticles were tested forantibacterial properties. Two polymers, Tecoflex FG-93A-B20 (W filament)and Isoplast 2510 (D filament), were provided and each were treated withsilver nanoparticles. FIGS. 5A-C illustrate STEM images of TecoflexEG-93A-B20 thermoplastic embedded with nanoparticles. FIGS. 6A-6Cillustrate STEM images of Isoplast 2510 thermoplastic embedded withnanoparticles. FIGS. 8A-B illustrate a silver nanoparticle embedded in athermoplastic.

The silver nanoparticles were manufactured in isopropyl alcohol at aconcentration of 38 mg/L (38 ppm). The alcohol mixture was applied topolymer beads or granules. The polymer beads or granules were melted fora final concentration of 6 mg/K (6 ppm) in the resulting PE polymer.This concentration of 6 mg/kg had previously been successful in surfaceantibacterial testing.

The alcohol was removed using a nitrogen blowdown system, leaving thenanoparticles distributed on the surface of the plastic beads. Thepolymer beads were then run through an extrusion melt system at 230° C.to form filaments. The nanoparticles on the surface of the polymer beadsintermixed into the filaments produced. The filaments were then embeddedin toming polymer and tomed to an 80-100 nm thickness and mounted on 200mesh formvar Carbon B TEM grids for imaging.

Imaging was performed on a JEOL 2800 Scanning Transmission ElectronMicroscope (STEM) with a darkfield camera, brightfield camera and asecondary surface camera. Element mapping to 1 nm² resolution wasperformed to identify nanoparticles and particulates, using a dual EDSdetector for triangulation and net count accuracy.

The Tecoflex FG-93A-B20 thermoplastic was light purple in color andrequired a clenching or cooling stage after melt extrusion at 230° C. Asshown in FIGS. 5A-C, under STEM, large solid metal particles hundreds ofnanometers in size were observed. EDS mapping revealed these to bebarium sulfate.

Silver nanoparticles directly interact with sulfur chemistry and theoverwhelming amount of barium sulfate (which is used as a filler andstiffener in Tecoflex FG-93A-B20) appears to have sequestered the silvernanoparticles. No direct nanoparticles were found on any grid from STEMimaging. Background silver was detected in the barium sulfate particles.Thermal disassociation was seen on the surface of the filaments, whichwas expected due to lack of thermal control in the final filamentformation.

The Isoplast 2510 thermoplastic was darker purple in color and moreglass like in surface finish. The Isoplast 2510 thermoplastic was meltedat 230° C. and cooled at room temperature (22.5° C.). This thermoplasticused a phosphate as a filler and stiffener instead of barium sulfate. Asshown in FIGS. 6A-C, the phosphates did not interact with the Agnanoparticles, and it was easy to find and element map the silvernanoparticles present. Isoplast 2510 is a more suitable candidate tocreate an equal distribution of the silver nanoparticles within theplastic. The surface did not have the same type of thermaldisassociation.

Concentrations of material to obtain the desired effect may be scaledappropriately. Further testing with several other plastics by similaranalytical methods as described herein is a continuing process dependingon the purpose and need of the material.

Example 3

Typical surface antibacterial testing is conducted using an acceptedstandard known as a peni-cylinder. The conventional peni-cylinder has anoutside diameter of 7.8 mm, an inside diameter of 5.8 mm and is 9.9 mmin length. The surface area can be calculated as:

A _(s)=(Outside surface area)+(inside surface area)+2(end surface area)

A _(s)=242.6 mm²+180.4 mm²+42 mm²

A _(s)=465 mm²

Because the ends of the peni-cylinder have a 45° taper, the overallsurface area is a little less than calculated but the difference isinconsequential.

20 mm long filament analogs to the peni-cylinder were used forantibacterial testing. The filament diameter was 1.2 mm and for every 1mm in length there is 7.5 mm² of outside surface area and an endssurface area of 2.3 mm². A 20 mm long filament has a total surface areaof A_(f)=152.3 mm². The total number of filaments at 20 mm long neededto represent a peni-cylinder are:

A _(s) /A _(f)=465/152.3=3.1

Three filaments were used in each testing sample set to approximatelyequal the surface area of one peni-cylinder surface. Metal nanoparticleswere suspended throughout each filament.

The filaments were cleaved with a straight edge disposable razor cleanedwith 70% or higher isopropyl alcohol. The filaments were measuredagainst a serial surface that has two marks 20 mm apart and thefilaments were cleaved to that length. The cut filaments weretransferred to a 50 mL sample tube containing 25 mL of isopropyl alcoholand vortexed for 1 minute. The filaments were then removed, usingtweezers that had been flame/heat sterilized, to a 50 mL sample holdingcontainer.

The antibacterial testing was performed using E. coli at levels of 10⁵,10⁶ and 10⁷ colony forming units (CFU). Each set of three filaments wereintroduced to the E. coli in tryptic soy broth for 1 hour of E. coliexposure. Two sample sets (of three filaments) were used for eachconcentration of E. coli.

The filaments were removed from the tryptic soy broth containing the E.coli colonies and allowed to drip until the filaments were free offluids. The filaments were then introduced to dey-engley (DE) broth witha purple color. If any E. coli bacteria grew from the filamentstransferred to the DE broth, the color of the broth would turn yellow.

Samples of the DE broth were cultured for any colony growth on trypticsoy agar plates and compared with the cultures of the originallyprepared 10⁵, 10⁶ and 10⁷ CFUs. Colony counts were then made after 24and 48 hours of growth. CFUs of the E. coli were verified by agarcounts: 10⁵=23 CFUs; 10⁶=256 CFUs; and 10⁷=1000 CFUs.

After 24 hours of testing there were 0 CFUs on any of the filament agarplates for all prepared concentrations of E. coli. After 48 hours oftesting there were 0 CFUs on any of the filament agar plates for allprepared concentrations of E. coli. The DE broth showed no color changefor all prepared concentrations of E. coli exposed to the filamentsafter 24 and 48 hours. There were no live bacteria on the surface of anyof the filaments that were exposed for 1 hour to E. coli concentrationsof the 10⁵, 10⁶ and 10⁷ CFUs. Duplicates of the testing showed the sameresults.

Example 4

A method was successfully employed to spray industry standard pellets,illustrated in FIG. 7A. The sprayed pellets were then extruded through ahot mixer into a filament, as illustrated in FIG. 7B. The filament wascross sectioned with a diamond edge cutter to under 100 nm thickness,after encasing in ECON polymer to protect the filament from damage.Tomed slices of the filament were used for STEM/EDS imaging. Thenanoparticles successfully integrated with the plastic and did show aninteresting, uniform distribution that was not exclusive with theplastic polymer chains. The nanoparticles appear to be free to moveabout the plastic if a fluid force and temperature or energy gradient ispresent.

Example 5

Spherical-shaped silver nanoparticles made by laser ablation so as tohave no external bond angles or edges and which are nonionic and do notrelease silver ions, were tested to determine if they caused silvernanoparticle resistant bacteria. No such resistance was detected after28 passages.

The study was entitled “Mutant generation testing on P. aeruginosa ATCC15442, and E. coli ATCC 25922”. Two different types of spherical silvernanoparticles were tested: Silver Lot # Desktop Laser: Ag200917-104 (19PPM) and Silver Lot # Industrial Laser: 171229-101 (16.8 PPM). Thespherical-shaped silver nanoparticles made by ablation using the desktoplaser had a narrow particle size distribution between 8-10 nm, and thespherical-shaped silver nanoparticles made by ablation using theindustrial laser had a slightly less narrow particle size distributionbetween 8-12 nm,

The procedure for the study is outlined as follows:

Bacteria Preparation

-   -   1. Streak bacteria onto tryptic soy agar (TSA) plates and        incubate overnight 37° C.    -   2. Next day, inoculate 10 mL of silver with Mueller Hinton broth        mix with one colony.        -   a. Desktop laser:            -   i. E. coli—Make a 4.75 ppm silver nanoparticle mix in                the broth (2.5 mL Ag+7.5 mL broth).            -   ii. P. aeruginosa—Make a 4.75 ppm silver nanoparticle                mix in the broth (2.5 mL Ag+7.5 mL broth).        -   b. Industrial laser:            -   i. E. coli—Make a 2 ppm silver nanoparticle mix in the                broth (1.2 mL Ag+8.8 mL broth).            -   ii. P. aeruginosa—Make a 2 ppm silver nanoparticle mix                in the broth (1.2 mL Ag+8.8 mL broth).    -   3. Incubate at 37° C. at 250 RPM 24-36 hours.    -   4. Monitor growth the next day.    -   5. Continue to serial passage in a new silver broth mixture with        an inoculating loop into culture.    -   6. Every 5-7 days, streak out a loop of culture onto TSA plates        to preserve passages then perform an MIC test on colonies to        measure if the bacteria have generated resistance to the        spherical silver nanoparticles.

The results of the study are as follows:

Results MIC Values:

-   -   E. coli—Industrial laser sample: MIC held at 2 ppm out to serial        passage 28.        -   DT laser sample: Culture stopped regenerating after            passage 21. MIC held in previous passages.    -   P. aeruginosa—Industrial laser sample: MIC held at 2 ppm out to        serial passage 28.        -   DT laser sample: Culture stopped regenerating after            passage 21. MIC held in previous passages.            All negative and positive controls passed.

Comparative Example

A similar test is made using conventional silver nanoparticles madeusing a chemical synthesis process. The silver nanoparticles haveexternal bond angles and edges and release silver ions in water. Within6 passages anti-silver resistance is apparent from increasing MICvalues.

Additional Terms & Definitions

While certain embodiments of the present disclosure have been describedin detail, with reference to specific configurations, parameters,components, elements, etcetera, the descriptions are illustrative andare not to be construed as limiting the scope of the claimed invention.

Furthermore, it should be understood that for any given element ofcomponent of a described embodiment, any of the possible alternativeslisted for that element or component may generally be used individuallyor in combination with one another, unless implicitly or explicitlystated otherwise.

In addition, unless otherwise indicated, numbers expressing quantities,constituents, distances, or other measurements used in the specificationand claims are to be understood as optionally being modified by the term“about” or its synonyms. When the terms “about,” “approximately,”“substantially,” or the like are used in conjunction with a statedamount, value, or condition, it may be taken to mean an amount, value orcondition that deviates by less than 20%, less than 10%, less than 5%,less than 1%, less than 0.1%, or less than 0.01% of the stated amount,value, or condition. At the very least, and not as an attempt to limitthe application of the doctrine of equivalents to the scope of theclaims, each numerical parameter should be construed in light of thenumber of reported significant digits and by applying ordinary roundingtechniques.

Any headings and subheadings used herein are for organizational purposesonly and are not meant to be used to limit the scope of the descriptionor the claims.

It will also be noted that, as used in this specification and theappended claims, the singular forms “a,” “an” and “the” do not excludeplural referents unless the context clearly dictates otherwise. Thus,for example, an embodiment referencing a singular referent (e.g.,“widget”) may also include two or more such referents.

It will also be appreciated that embodiments described herein may alsoinclude properties and/or features (e.g., ingredients, components,members, elements, parts, and/or portions) described in one or moreseparate embodiments and are not necessarily limited strictly to thefeatures expressly described for that particular embodiment.Accordingly, the various features of a given embodiment can be combinedwith and/or incorporated into other embodiments of the presentdisclosure. Thus, disclosure of certain features relative to a specificembodiment of the present disclosure should not be construed as limitingapplication or inclusion of said features to the specific embodiment.Rather, it will be appreciated that other embodiments can also includesuch features.

1. A method of manufacturing nanoparticle-embedded polymer-basedproducts, the method comprising: applying a nanoparticle solution topolymer granules, the nanoparticle solution comprising metalnanoparticles, and a volatile solvent; heating the polymer granulescontaining the nanoparticle solution, wherein heating the polymergranules causes the volatile solvent to evaporate, wherein heating thepolymer granules causes the metal nanoparticles to uniformly dispersethroughout a molten polymer; and forming the molten polymer with auniform distribution of metal nanoparticles into a plastic-basedproduct, wherein the plastic-based product is embedded with the metalnanoparticles.
 2. The method of manufacturing of claim 1, wherein themetal nanoparticles comprise silver nanoparticles.
 3. The method ofmanufacturing of claim 1, wherein the metal nanoparticles comprise goldnanoparticles.
 4. The method of manufacturing of claim 1, wherein themetal nanoparticles comprise a combination of gold and silvernanoparticles.
 5. The method of manufacturing of claim 1, wherein theembedded nanoparticles in the plastic-based product are configured todown-shift incoming UV radiation.
 6. The method of manufacturing ofclaim 5, wherein the embedded nanoparticles down shift incoming UVradiation by at least about 50 nm, or at least about 100 nm, or at leastabout 150 nm, such as by approximately 200 nm.
 7. The method ofmanufacturing of claim 1, wherein the volatile solvent is selected fromthe group consisting of ethanol, isopropyl alcohol, and acetone.
 8. Apolymer composition comprising: a nanoparticle solution comprising avolatile solvent and metal nanoparticles; and a plurality of polymerpellets coated with the nanoparticle solution.
 9. The polymercomposition of claim 8, wherein the metal nanoparticles comprise silvernanoparticles.
 10. The polymer composition of claim 8, wherein the metalnanoparticles comprise gold nanoparticles.
 11. The polymer compositionof claim 8, wherein the metal nanoparticles comprise silver and goldnanoparticles.
 12. The polymer composition of claim 11, wherein a ratioof silver to gold nanoparticles is 1:1 to about 50:1, or about 2.5:1 toabout 25:1, or about 5:1 to about 20:1, or about 7.5:1 to about 15:1, orabout 9:1 to about 11:1, or about 10:1.
 13. The polymer composition ofclaim 8, wherein the metal nanoparticles are in the size range of 1 to40 nm, or 10 to 30 nm, or 15 to 20 nm.
 14. The polymer composition ofclaim 8, wherein the metal nanoparticles are present in a concentrationof 1 to 15 ppm, or 1.5 to 10 ppm, or 2 to 5 ppm.
 15. A multi-partcurable resin comprising: a first component of the multi-part curableresin; a second component of the multi-part curable resin; and metalnanoparticles combined with one or both of the first and secondcomponents.
 16. The multi-part curable resin of claim 15, wherein themulti-part curable resin is selected from epoxy, silicone, andurethane-based.
 17. The multi-part curable resin of claim 15, whereinthe metal nanoparticles are selected from silver nanoparticles, goldnanoparticles, and mixture thereof.
 18. The multi-part curable resin ofclaim 15, wherein the metal nanoparticles are spherical.
 19. Themulti-part curable resin of claim 18, wherein the spherical metalnanoparticles are selected from the group consisting of silvernanoparticles, gold nanoparticles, and mixture thereof.
 20. Themulti-part curable resin of claim 15, wherein the metal nanoparticlesare coral-shaped.